American Scientist

Recognized internationally for her contributions to the field of virology, Anna Marie Skalka has conducted research to understand viruses’ many functions—both harmful and helpful—and has described their evolutionary role in our species. She is recipient of the 2018 Sigma Xi William Procter Prize for Scientific Achievement, an annual lifetime achievement award established in 1950 by an heir of one of the founders of the Procter and Gamble Company. Previous awardees include engineer Vannevar Bush, physicist Leon Lederman, and behaviorist Jane Goodall, among many others. American Scientist’s digital managing editor, Robert Frederick, spoke with Skalka about her work and big data’s emerging role in the field of virology.

Over your career, you’ve seen a lot of changes to the field of virology. Have there been any surprises?

Oh yes! When the first human genome was made available in the early 2000s, I was very surprised by the fact that 8 percent of our genome is actually retroviral sequences—that’s really a shocking number. That’s more genetic information than is contained in all of the exons that encode all the proteins in our bodies, which is only about 1 percent of our genome.

In some cases these retroviral sequences have been co-opted for our benefit. They’ve been conserved. One of the most striking examples is in the formation of the mammalian placenta. I don’t know how many people know that the formation of the placenta depends on a retroviral protein. It’s the protein that makes the envelope of the virus and it’s been co-opted in human genetics to make the placenta. If we didn’t have that protein, we might be laying eggs, like chickens.

Some of the tools that have become available during your career include all the ways science is being done with computers. How have you seen for yourself computer tools being employed in virology?

I went for a sabbatical at the Institute for Advanced Study in Princeton, to a department called the Simons Center for Systems Biology, which is chaired by Arnie Levine. His idea was to put biologists together with people who did bioinformatics. I worked with Vladimir Belyi, who is a genomics person, but a physicist, really. Together we decided to look to see whether there were any other viral genes in vertebrate DNAs.

What we did was to take all of the vertebrate sequences that were known at the time, in 2009, so there were about 48 vertebrate sequences of various species known. We chose to look first for viral genes from viruses that have RNA genomes but are not retroviruses. There are 16 different families of these. So Vladimir ran all of their genomes against all of the vertebrate genomes, and what we found was really astounding: There were, I think, something like 80 genes of these various viruses, in the sequences of about 16 of these vertebrate species.

The most interesting part is that there are 16 RNA viruses, but the genes were only from two viral families: They were filoviruses (the genus that includes Ebola virus and Marburg virus), and Bornaviruses, which include Borna disease virus. Then, when we looked at phylogenetic trees, we discovered that these viral sequences were integrated something like 40 million years ago, most of them. And more surprisingly, some of these sequences were conserved throughout evolution. And the proteins were actually made in some of the species that have these genes in them.

What is it about these two viral families —with Ebola and Borna—that makes them so special that their genes ended up in vertebrates?

They’re both very highly pathogenic. We all know about Ebola virus, which causes a terrible hemorrhagic disease. I think the fatality rate is 50 to 90 percent. Borna virus is equally fatal for the species it infects—horses, cloven-hoofed animals, some dogs, and so forth. There it’s 80 percent fatal. So we decided maybe this conservation has something to do with the pathology.

Well, we found a very interesting correlation: Those species that were natural hosts to these Borna viruses, none of them contained any genes from these viruses in their DNA. But those species that were not natural hosts contain the genes. And then we thought, “Maybe these genes are some sort of genetic immunization against infection with the virus.” That was just an idea that we put out at the time, but since then it has actually been verified for squirrels. Now, the squirrels have a Borna virus disease gene in them, put in there something like 10 million years ago, so it’s pretty new. It turns out that if you express that gene in cells and then infect them with Borna virus, the Borna virus will not grow.

It’s really been fascinating. Actually, I think it contributed to a whole new field called paleovirology. There’s even a journal now for it. And it was a real acknowledgement that, really, viruses are us. We are viruses walking around, for better or for worse.

So by trying to defeat some viruses we could be unintentionally—but potentially—hurting human health?

Well, yes. Because viruses, they have two facets. Some of them are bad and some of them are good. And this genetic exchange, of which they are mediators, is important to evolution. And you can see that some of the genes that are useful are conserved. And I think if you didn’t have this exchange, you would put a damper on some beneficial aspects of evolution.

A podcast based on an audio interview with Anna Marie Skalka: